Evaluation of the anti-fatigue effects of a traditional herbal drug, Gongjin-dan, under insufficient sleep conditions: study protocol for a randomised controlled trial.

Mi Ju Son,Young-Eun Kim,Jun-Hwan Lee,Chang-Gue Son,Hwi-Jin Im,Boncho Ku

doi:10.1186/s13063-016-1542-7

Abstract

BackgroundMany herbal medicines are traditionally used as anti-fatigue agents in east Asian countries; however, there is a dearth of clinical evidence supporting the anti-fatigue effects of such medicines and their mechanisms. This study is a feasibility trial to assess the clinical efficacy of Gongjin-dan (GJD) and verify its mechanisms by exploring fatigue outcomes, including endocrine and immunological biomarkers in humans.Methods/DesignTo investigate the anti-fatigue effects of GJD and the mechanism underlying these effects, a randomised, double-blind, placebo-controlled crossover clinical trial was designed. Participants (24 healthy male volunteers) will be hospitalised for 4 days (3 nights), during which acute fatigue and stress conditions will be induced by sleep deprivation, and GJD or a placebo will be administered (twice daily). The primary outcome will be changes in serum cortisol levels, measured in the morning, as an objective biomarker of sleep deprivation-induced fatigue and stress. The secondary outcomes will include: the Fatigue Severity Scale; the Brief Fatigue Inventory, and the Leeds Sleep Evaluation Questionnaire scores; levels of salivary cortisol, epinephrine, norepinephrine, oxidative stress-related biomarkers, homocysteine, and immunological factors; and heart rate variability. After a washout period of more than 4 weeks, a second treatment phase will commence in which participants who were previously administered the placebo will receive the drug and vice versa, following the same treatment regime as in the first phase.DiscussionThis study protocol provides a unique opportunity to enhance our understanding of fatigue and the effects of GJD on fatigue in terms of endocrine and immunological mechanisms by validating the study design and determining feasibility. Findings from this trial will help researchers to design a pilot or definitive clinical trial of traditional herbal medicine for chronic fatigue.Trial registrationKorean National Clinical Trial Registry CRIS; KCT0001681, registered on 29 October 2015.

Highlights

Many herbal medicines are traditionally used as anti-fatigue agents in east Asian countries; there is a dearth of clinical evidence supporting the anti-fatigue effects of such medicines and their mechanisms
This study protocol provides a unique opportunity to enhance our understanding of fatigue and the effects of GJD on fatigue in terms of endocrine and immunological mechanisms by validating the study design and determining feasibility
The aim of this study was to develop a protocol to (1) evaluate the anti-fatigue effects of GJD in acute fatigue; (2) verify the mechanisms underlying the observed effects by assessing changes in stress hormones, oxidative stress-related biomarkers, homocysteine, and immunological factors; and (3) clinically assess the effectiveness and safety of GJD in treating acute fatigue using the Korean version of the Fatigue Severity Scale (FSS-K), Brief Fatigue Inventory (BFI-K), and Leeds Sleep Evaluation Questionnaire (KMLSEQ) scores as well as carrying out daily fatigue and sleep evaluations and assessments of heart rate variability (HRV) and adverse events

Summary

Introduction

Many herbal medicines are traditionally used as anti-fatigue agents in east Asian countries; there is a dearth of clinical evidence supporting the anti-fatigue effects of such medicines and their mechanisms. Fatigue is a multifactorial condition and the pathophysiological mechanisms of idiopathic chronic fatigue or chronic fatigue syndrome are unclear For this reason, there is no standard treatment for chronic fatigue [4] and some patients with chronic fatigue, turn to complementary and alternative medicine (CAM) for treatment [5, 6]. In East Asian countries, CAM in the form of traditional herbal medicine is widely used to treat fatigue [7, 8]; the traditional herbal drug, Gongjin-dan (GJD), is generally prescribed by Korean traditional medicine physicians to treat patients with chronic fatigue in Korean traditional medicine clinics. To encourage evidence-based practices in the traditional medicine field, well-designed studies must be conducted to evaluate the effects and mechanisms of action of traditional herbal medicines, including traditional anti-fatigue medicines

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